Tissue engineering is a strategy for repairing or regenerating tissue. Cell culture in the context of tissue engineering further requires a three-dimensional scaffold for cell support. A scaffold having a three-dimensional porous structure is a prerequisite in many tissue culture applications as these cells would otherwise lose their cellular morphology and phenotypic expression in a two-dimensional monolayer cell culture.
An important issue in tissue regeneration and repair is the fabrication of three-dimensional scaffolds in such a manner that they mimic the extracellular matrix and thereby encourage the cells to grow functional tissues and allow the diffusion of nutrients, metabolites and soluble factors.
When regenerating tissue, the properties of the three-dimensional matrix can greatly affect cell adhesion and growth, and determine the quality of the final product. An optimal scaffold material would promote cell adhesion, cell proliferation, expression of cell-specific phenotypes, and the activity of the cells.
Biological materials have been used as scaffolding material in many tissue engineering applications and within the field of regenerative medicine to control the function and structure of engineered tissue by interacting with transplanted cells. These materials include naturally derived materials such as collagen and alginate. Some biological materials have been proven to support cell ingrowth and regeneration of damaged tissues with no evidence of immunogenic rejection, and encourage the remodelling process by stimulating cells to synthesize and excrete extracellular matrix proteins to aid in the healing process. Extracellular matrix components preserved in these biological materials are also able to influence the phenotypic differentiation of stem cells through specific interactions with e.g. cell surface receptors. However, the usage of such isolated biological materials is limited because of insufficient mechanical properties upon implantation and during perfusion cell seeding.
High porosity of the scaffold is generally recommended to reduce the amount of implanted material and to generate a large surface on to which the cells can adhere. Moreover, interconnectivity, the connection between the pores in the scaffold, is very important since it plays a decisive role in cell mobility within the scaffold and afterwards in the transport (diffusion and convection) of nutrients and cellular waste products.
Heijkants et al. (2008) discloses the manufacture of a porous scaffold from polyurethane by a combination of salt leaching and thermally induced phase separation. The method makes it possible to obtain a very porous foam material with a very high interconnectivity. A major advantage is that variables like porosity, pore size, and interconnectivity can be independently adjusted with the absence of toxic materials in the production process. However, an increase in the porosity of the resulting foam decreases the mechanical stability of the scaffold.
WO2006093778 discloses a solid freeform fabrication method of creating a three-dimensional article built at least in part from scaffolding layers. The method includes providing a scaffolding material and a supporting material. The supporting material is in the shape of a foamy layer. The foam is used as a support for the scaffolding material during preparation of the scaffold and subsequently removed by washing. In certain embodiments of the method, the foam is not removed, but is retained within the structure. WO2006093778 states that the problem with retaining the foam within the structure is that it traps air and may be restrictive to cell migration and travel. Additionally, for the printing device to be able to print directly into the foam, the foam has to be pliable for the nozzle of the printing device to be submerged. Therefore, the foam cannot be of the polymer type disclosed in the paper by Heijkants et al.
Mo et al. (2006) discloses a hollow PCL-PLGA composite tubular scaffold for blood vessel tissue engineering. This scaffold comprises a hollow PLGA braided tube coated with PCL; obtained by coating the braided tube with a PCL dioxane/water solution and then freeze-drying after phase separation. The hollow structure of the braided tube makes it especially vulnerable towards compressive forces under preparation, insertion and use.
Thus, it is an object of the present invention to improve the properties of a three-dimensional scaffold for its use in tissue engineering. In particular, an improved mechanical stability of the scaffold would be advantageous. More specifically, an improved compressive mechanical stress of the scaffold under preparation (e.g. cutting), insertion and use (e.g. when implanted) would be advantageous. Furthermore, improved cell mobility within the scaffold and transport of nutrients and cellular waste products would be advantageous.